Andrea Kasinski's Biography

Andrea Kasinski,
William and Patty Miller, Assistant Professor of Biological Sciences,
Purdue University

I serve as the William and Patty Miller Assistant Professor of Biological Sciences at Purdue University. My laboratory works on non-coding RNA biology and therapeutics. Specifically, we focus on identifying biologically important RNAs whose misexpression drives the tumorigenic process. We then utilize this information to design, develop, and implement RNA-based therapeutics. My expertise spans both non-coding RNA discovery and the use of pre-clinical genetically engineered mouse models (GEMM) of cancer. I have worked to streamline tumor formation in GEMMs, and used histology, luciferase expression, MRI, and CT to monitor primary and metastatic tumor progression in these models pre- and post-therapeutic intervention (Cancer Research, 2012, Oncogene, 2015). I have also generated primary tumor cultures from the Kras;p53 model that we and others are currently using to screen miRNA-based candidate therapeutics prior to using the miRNAs in vivo (Cancer Research, 2012 and Bio-Protocols, 2013). In my current work, our lab uses these models and other relevant cancer models to evaluate miRNA-based therapies and other therapeutic regiments as a combined effort with collaborators to dissect the diverse molecular events that occur from cancer initiation through development of metastatic disease, and to identify miRNAs that drive cancer initiation and progression. I have shown efficacy in multiple murine models for both lentiviral-miR-34 (Cancer Research, 2012) and systemically delivered miR-34 (Oncogene, 2015). I have reported over 40% increase in survival of mouse models of cancer following treatment with miR-34. The studies I have performed thus far have been instrumental in advancing MRX34, the first miRNA therapeutic, into clinical trial in collaboration with Dr. Andreas Bader, Vice President of Research and Development at Mirna Therapeutics. While I continue to evaluate miRNAs and other non-coding RNAs for therapeutic advancement I am also actively involved in identifying, developing, and testing novel small RNA delivery platforms. My group, in collaboration with Dr. Philip Low’s laboratory, determined that miRNAs need not be protected in vivo. Our data support the use of vehicle-free delivery of miRNAs to both breast and lung cancer cells in vitro and in vivo (FolamiRs: ligand targeted microRNA replacement therapy, under peer-review Science Translational Medicine).

MicroRNAs are small non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. Because elevations or reductions in microRNA levels can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, we introduce a novel delivery platform that delivers microRNAs in the absence of a protective vehicle. The method relies on the direct attachment of a microRNA to folate (FolamiR). Folate mediates the delivery of the conjugated microRNA into cells that overexpress the folate receptor (FR), a feature commonly found in multiple cancers. Using this strategy, we show that a specific tumor suppressive FolamiR, FolamiR-34a, is quickly taken up by human triple-negative breast cancer cells, in culture and in vivo, and slows their progression, and demonstrate efficacy in an aggressive Kras;p53 non-small cell lung cancer mouse model. These findings suggest that this first-in-class method of delivering microRNAs directly to tumors in vivo, without the use of toxic delivery vehicles, represents an exciting advance in the pursuit to develop non-toxic, targeted therapeutics with promising clinical efficacy.